Staging in colorectal cancer (CRC) is critical to determining the extent of disease, guiding treatment decisions, and establishing prognosis. Once a diagnosis is confirmed, a structured evaluation must be performed to assess local and distant spread before deciding on further management. This comprehensive guide integrates all essential components of CRC staging used in clinical practice.
Histologic Review Before Staging
Before initiating staging procedures or considering surgery, it is essential to review the pathology of the biopsy specimen—especially when dealing with malignant polyps. If a malignant polyp is completely excised and lacks high-risk histological features (e.g., positive margins, poor differentiation, lymphovascular invasion), further resection may not be necessary. This assessment is more feasible when the polyp is pedunculated.
TNM Staging System: AJCC/UICC 8th Edition
The TNM (Tumor, Node, Metastasis) classification, jointly endorsed by the American Joint Committee on Cancer (AJCC) and Union for International Cancer Control (UICC), is the global standard for CRC staging. Older systems such as the Astler-Coller modification of Duke’s classification are now discouraged and not universally used.
Key Updates in the 8th Edition:
- M1c category introduced for peritoneal carcinomatosis, acknowledging its poor prognosis.
- Nodal micrometastases (>0.2 mm) are now classified as node-positive due to their adverse prognostic impact.
- Clarifications were made regarding tumor deposits and their relevance to nodal classification.
Prognostic and Treatment-Influencing Factors Outside TNM
Several clinical and pathological parameters, although not formally part of the TNM system, critically inform management:
- Preoperative CEA (Carcinoembryonic Antigen) levels.
- Tumor regression score (TRS) post-neoadjuvant therapy, especially in rectal cancer.
- Circumferential resection margin (CRM) involvement in rectal cancer.
- Lymphovascular and perineural invasion, both linked to poorer outcomes.
- Microsatellite instability (MSI) and Mismatch repair deficiency (dMMR):
- Prognostically favorable.
- Predictive of poor response to fluoropyrimidine therapy.
- Indicative of potential response to immune checkpoint inhibitors.
- Tumor border configuration and tumor budding, both associated with aggressive tumor biology.
Clinical vs. Pathologic Staging
Staging can be clinical (preoperative) or pathologic (post-resection):
- Clinical staging relies on radiologic, endoscopic, and surgical findings.
- Pathologic staging (pT, pN, pM) is based on histologic examination of resected tissue.
- In cases of neoadjuvant therapy, especially for rectal cancers, the prefix yp (e.g., ypT, ypN) denotes post-treatment pathologic stage.
Clinical Staging: Evaluation Protocol
Initial Evaluation
- A detailed physical examination.
- Contrast-enhanced CT scan of the chest, abdomen, and pelvis is the cornerstone of staging for metastatic disease.
Laboratory Tests
- Liver function tests may be ordered but are unreliable in detecting small hepatic metastases. Among these, alkaline phosphatase elevation is most suggestive of hepatic involvement.
Imaging Modalities in CRC Staging
Computed Tomography (CT)
The standard staging modality used in most institutions (especially for stage II-IV CRC):
- Abdominal and pelvic CT identifies:
- Regional tumor extension.
- Lymphatic and distant metastases.
- Complications like obstruction, perforation, or fistulas.
Sensitivity:
-
- Distant metastases: 75–87%
- Nodal involvement: 45–73%
- Depth of wall invasion: ~50%
- Perirectal adenopathy in rectal cancer is presumed malignant due to low incidence of benign nodes unless inflammatory disease is present.
- Limitations in Peritoneal Disease:
- Sensitivity for nodules <0.5 cm: ~11%
- Sensitivity for 0.5–5 cm: ~37%
CT may not reliably detect low-volume peritoneal metastases.
- Timing of CT: Preferably preoperative to impact surgical decision-making.
Pelvic MRI
- Gold standard for rectal cancer staging.
- Superior in assessing:
- Tumor depth.
- Nodal involvement.
- Circumferential resection margin (CRM).
CT of the Chest
- May be more relevant in rectal cancer due to venous drainage bypassing the liver.
- Frequent discovery of indeterminate pulmonary nodules (IPNs) (10–30%) with only 7–20% turning out to be malignant.
Risk Factors for Malignant IPNs:
- Size ≥5 mm.
- Multiple nodules.
- Non-subpleural location.
- Rectal origin (vs colon).
- Presence of distant metastases.
- Lack of calcification (which suggests benignity).
A large systematic review of 5873 patients found:
- 9% had IPNs.
- 11% of those were confirmed as metastatic at follow-up.
Liver MRI
- More sensitive than CT for identifying liver metastases, especially in fatty liver.
- Used selectively when CT is inconclusive or for precise hepatic lesion mapping.
- Triple-phase CT has improved, but MRI remains preferred for uncertain or borderline resectable liver lesions.
PET and PET/CT Scanning
- Not recommended for routine staging.
- Indications:
- Rising CEA levels with non-diagnostic conventional imaging (to detect recurrence).
- Evaluation before liver resection (to exclude extrahepatic disease).
Limitations:
- Recent chemotherapy can reduce PET sensitivity.
- PET is best performed before systemic therapy when liver resection is a possibility.
A randomized study found that PET-CT changed surgical management in 8% but had no effect on long-term survival.
Locoregional Staging in Rectal Cancer
Pre-treatment staging in rectal cancer is critical to determine:
- Tumor location in the rectum.
- Extent of spread.
- Appropriateness for local excision, radical resection, or neoadjuvant therapy.
Tools:
- Digital rectal examination
- Rigid sigmoidoscopy
- Transrectal ultrasound (TRUS)
- Endoscopic ultrasound (EUS)
- Pelvic MRI
These assist in evaluating CRM involvement and nodal status, guiding decisions regarding the use of preoperative chemoradiation or systemic therapy.
Surgical and Postoperative Considerations
In colon cancer, surgical resection is typically followed by:
- Pathologic staging of the resected specimen to determine:
- Tumor depth (T)
- Nodal status (N)
In cases of hepatic metastases:
- The presence of up to four liver lesions may still permit curative resection.
- Simultaneous vs. staged resection is debated, with some centers performing synchronous surgeries depending on tumor burden and symptoms.
Conclusion
Colorectal cancer staging is a multifaceted process involving histopathology, radiologic imaging, molecular profiling, and surgical evaluation. The TNM system remains the staging cornerstone, but clinicians must also account for a range of biologic and clinical factors not encompassed by TNM alone. Imaging advances and molecular diagnostics continue to refine staging accuracy, enabling personalized, evidence-based treatment planning for improved patient outcomes.
